RETINOBLASTOMA RELATED 1 switches mitosis to meiosis in rice.

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.

Interstage Survival for Patients with Hypoplastic Left Heart Syndrome After ECMO.

There is a reported 5-20 % incidence of extracorporeal membrane oxygenation (ECMO) following stage I palliation for hypoplastic left heart syndrome (HLHS). This study compares the interstage mortality of HLHS patients supported with ECMO (HLHS-ECMO) to those who were not supported with ECMO (HLHS-nECMO) using the National Pediatric Cardiology Quality Improvement Initiative database. Patients with HLHS who survived to hospital discharge after stage I palliation were analyzed. HLHS-ECMO patients were compared to HLHS-non-ECMO patients with respect to demographics, surgical variables, and interstage survival. A total of 931 patients were identified in the database. Sixty-six (7.1 %) patients were supported with ECMO during their stage I palliation admission. There were no statistically significant differences between the groups with respect to demographics or anatomic subtype. HLHS-ECMO patients were more likely to have a preoperative risk factor identified (62 vs. 48 %, p = 0.03) or require ECMO prior to stage I palliation (3 vs. 0.5 %, p = 0.03). HLHS-ECMO patients had a significantly higher incidence of death or transplant versus the HLHS-nECMO group (18 vs. 9 %, p = 0.03). Despite survival to discharge, patients with HLHS requiring ECMO after their palliation continue to have an increased risk of death/cardiac transplant versus patients that do not require ECMO. ECMO use is likely a marker for a high-risk patient group. These patients may benefit from closer follow-up during the interstage period.

Isolated heart transplant and combined heart-liver transplant in adult congenital heart disease patients: Insights from the united network of organ sharing.

BACKGROUND/METHODS: The aging patient with severe congenital heart disease (CHD) faces many challenges: heart failure, arrhythmia, and in the Fontan patient, liver disease. Our goal was to define combined heart liver transplant (CHLT) and isolated orthotopic heart transplant (OHT) outcomes in U.S. adult CHD patients. The U.S. United Network for Organ Sharing (UNOS) thoracic and liver databases were queried for cardiac and CHD diagnoses, from inception-2014. RESULTS: In CHLT, CHD made up 22% of waitlist patients (non-CHD n=262 vs. CHD n=58), and 20% of transplanted patients (non-CHD n=137 vs. CHD n=27). Liver function tests in the non-CHD and CHD groups were similar and there was no difference in CHD and non-CHD survival (HR 0.93, CI: 0.36-2.38, p 0.48). In isolated OHT, CHD patients comprised 2% of those listed (non-CHD n=74,080 vs. CHD n=1599) and transplanted (non-CHD n=48,985 vs. CHD n=967) and had higher early (<1year) mortality (HR 1.36, CI: 1.18-1.57, p<0.0001), but better long-term survival (HR 0.66, CI; 0.57-0.76, p<0.001) than non-CHD. Both groups benefitted from mechanical support when used (non-CHD HR 0.34, CI: 0.31-0.37 and CHD HR 0.14, CI: 0.03-0.58) and prior sternotomy had no effect on mortality in CHD (HR 0.63, CI: 0.15-2.58). CONCLUSIONS: Survival of CHD patients undergoing CHLT is no different than in non-CHD, encouraging consideration of CHLT when clinically appropriate. Short-term mortality is higher in CHD (vs. non-CHD) patients undergoing OHT, regardless of prior cardiac surgery status. Modifications to CHD classification within UNOS would help better understand CHD CHLT and OHT outcomes.

Arrhythmias After Stage I Hybrid Palliation in Single-Ventricle Patients.

The hybrid procedure is an alternative palliative strategy for patients with single-ventricle physiology. No data exist documenting the incidence of arrhythmias after the hybrid procedure. Goal of this study was to determine the incidence and type of arrhythmias in patients undergoing the hybrid procedure. A retrospective chart review was performed including all patients undergoing the hybrid procedure between January of 2010 through December of 2013. Sixty-five patients underwent the hybrid procedure during this time period (43 HLHS, 22 other). Average gestational age at admission was 37.7 weeks. Average age at time of procedure was 7.6 days. Five patients had documented arrhythmias (7.7 %). Four were supraventricular tachycardias, and 1 was a sinus bradycardia. One patient with arrhythmia died during hospitalization, and another patient with arrhythmia died during the interstage period. Hybrid palliation for patients with single-ventricle physiology has a low incidence of arrhythmias. In this cohort of patients, arrhythmias did not contribute to mortality. There was a trend toward association between arrhythmias and longer total length of hospital stay.

Changes in right ventricular function in neonates with hypoplastic left heart syndrome before and after the hybrid procedure.

AIMS: Decreased right ventricular function via deformation analysis has been noted in patients with hypoplastic left heart syndrome (HLHS) after the Norwood procedure. No data exist in HLHS patients undergoing the hybrid procedure. The goal of this study was to evaluate right ventricular functional changes in HLHS patients undergoing the hybrid procedure under steady-state conditions. METHODS AND RESULTS: Echocardiograms were prospectively obtained on patients with HLHS before and after the hybrid procedure. Fractional area change, tricuspid inflow velocities, tissue Doppler imaging (TDI), and deformation analysis were performed. Paired Wilcoxon's signed rank or Student's t-test was used for analysis. P < 0.05 was considered significant. Twenty HLHS patients were studied (10 males:10 females). Median age at the pre-hybrid echocardiogram was 3 (1-16) days, age at hybrid procedure was 5 (3-17) days, and age at post-hybrid echocardiogram was 10 (6-34). There were significant decreases in systolic function as measured by TDI and deformation analysis. There was no significant change in right ventricular fractional area change. Diastolic function was also noted to significantly decrease after the hybrid procedure. CONCLUSION: Systolic and diastolic functions decreased after the hybrid procedure despite the fact that patients avoided cardiopulmonary bypass. These results are comparable with previous reports in HLHS patients undergoing the Norwood procedure. Further studies are needed to determine if these echocardiographic changes have prognostic significance.

Cost-benefit analysis of robotic versus nonrobotic minimally invasive mitral valve surgery.

OBJECTIVE: To date, a direct comparison of minimally invasive mitral valve repair or replacement (mini-MVR) versus robotic MVR is lacking; therefore, the purpose of this study was to address this deficit and compare mini-MVR with robotic MVR from a cost-benefit perspective. METHODS: From a total of 759 literature citations, 21 studies were included for statistical comparisons of benefit outcomes, whereas 3 studies and our institutional experience were used to compare costs. RESULTS: The total cost per case exceeding that of conventional MVR is approximately $2063.90 for robotic MVR and $271 for mini-MVR. Mean 30-day mortality rates for mini-MVR and robotic MVR groups were 1.24% and 0.55%, respectively [106/8548 vs 6/1089; odds ratio (OR), 2.27; P = 0.052]. The conversion rate to conventional MVR was 0.77% in mini-MVR and 1.83% in robotic MVR (35/5092 vs 22/1046; OR, 0.32; P < 0.001). The rate of neurologic events was 1.32% in mini-MVR and 2.37% in robotic MVR (109/8257 vs 20/845; OR, 0.55; P = 0.02). Postoperative atrial fibrillation was seen in 11.42% of mini-MVR patients and in 19.67% of robotic MVR patients (371/3249 vs 203/1032; OR, 0.53, P < 0.001). Mean cardiopulmonary bypass time was longer in mini-MVR (137.4 vs 130.4 minutes), whereas cross-clamp time was shorter (82.2 vs 96.7 minutes). CONCLUSIONS: Our comparative analysis provides insights into the clinical benefits versus variable costs relationship related to mini-MVR and robotic MVR.

Neurodevelopmental outcome after cardiac surgery utilizing cardiopulmonary bypass in children.

INTRODUCTION: Modulating the stress response and perioperative factors can have a paramount impact on the neurodevelopmental outcome of infants who undergo cardiac surgery utilizing cardiopulmonary bypass. MATERIALS AND METHODS: In this single center prospective follow-up study, we evaluated the impact of three different anesthetic techniques on the neurodevelopmental outcomes of 19 children who previously underwent congenital cardiac surgery within their 1(st) year of life. Cases were done from May 2011 to December 2013. Children were assessed using the Stanford-Binet Intelligence Scales (5(th) edition). Multiple regression analysis was used to test different parental and perioperative factors that could significantly predict the different neurodevelopmental outcomes in the entire cohort of patients. RESULTS: When comparing the three groups regarding the major cognitive scores, a high-dose fentanyl (HDF) patients scored significantly higher than the low-dose fentanyl (LDF) + dexmedetomidine (DEX) (LDF + DEX) group in the quantitative reasoning scores (106 ± 22 vs. 82 ± 15 P = 0.046). The bispectral index (BIS) value at the end of surgery for the -LDF group was significantly higher than that in LDF + DEX group (P = 0.011). For the entire cohort, a strong correlation was seen between the standard verbal intelligence quotient (IQ) score and the baseline adrenocorticotropic hormone level, the interleukin-6 level at the end of surgery and the BIS value at the end of the procedure with an R(2) value of 0.67 and P < 0.04. There was an inverse correlation between the cardiac Intensive Care Unit length of stay and the full-scale IQ score (R = 0.4675 and P 0.027). CONCLUSIONS: Patients in the HDF group demonstrated overall higher neurodevelopmental scores, although it did not reach statistical significance except in fluid reasoning scores. Our results may point to a possible correlation between blunting the stress response and improvement of the neurodevelopmental outcome.

Minimally Invasive Aortic Valve Replacement: Cost-Benefit Analysis of Ministernotomy Versus Minithoracotomy Approach.

BACKGROUND AND AIM OF THE STUDY: Minimally invasive aortic valve replacement via ministernotomy (ministernotomy-AVR) or minithoracotomy (minithoracotomy-AVR) is gaining popularity. To date, a direct comparison of ministernotomy-AVR versus minithoracotomy-AVR is lacking. The study aim was to compare these two procedures from a cost-benefit perspective. METHODS: Eight reports from the United States were selected from amongst 33,494 literature citations based on sample size and data completeness. Perioperative variables were collected for each surgical approach. Fixed and variable costs were estimated as cost per case in excess of full sternotomy AVR procedures. RESULTS: Ministernotomy-AVR patients were of a significantly lower mean age (59.8 years versus 67.9 years), ejection fraction (50.4-51.6% versus 56.1-57.8%), shorter cardiopulmonary bypass time (97.2 min versus 125.6 min) and cross-clamp time (69.9 min versus 87.9 min), a lower rate of blood transfusion (25.9% versus 64.4%), and a shorter length of hospital stay (5.7 versus 6.2 days). There were no significant inter-group differences in 30-day mortality, conversion to sternotomy, neurologic events, arrhythmia, wound infection, or postoperative bleeding. Assuming a volume of 50 cases per year, the added operative cost per case for a minithoracotomy-AVR was US$ 4,254 compared to US$ 290 for a ministernotomy-AVR. The added costs per case, assuming 200 cases per year, were US$ 4,209 and US$ 290, respectively. A minithoracotomy-AVR program performing 50 cases per year adds US$ 1,063,665 of operative costs over five years, compared to US$ 72,500 for a ministernotomy-AVR program. CONCLUSION: The present analysis suggested that the clinical benefits of ministernotomy-AVR are comparable or better than those of minithoracotomy-AVR, and at lower costs. Healthcare delivery organizations should consider the results of cost-benefit examinations when developing surgical valve replacement programs.

Plethysmography variability index response to isovolemic hemodilution in children prior to surgery for congenital heart disease.

The aim of this study was to evaluate the response of pleth variability index (PVI) to phlebotomy in anesthetized children prior to surgery for congenital heart disease. After induction of general anesthesia and prior to surgical incision, approximately 10 mL/kg of blood was removed from 40 mechanically ventilated children over a 5-10 min period. The PVI was continuously monitored. Additionally, the volume of crystalloid required to ensure hemodynamic and near infrared spectroscopy stability was recorded. There was no difference between the pre-phlebotomy PVI (13% ± 6.2) and the post-phlebotomy PVI (16.4% ± 9.6) (P = 0.55). Patients who had a starting PVI ≤14% had a significant increase in PVI after phlebotomy from 9.1% ± 3 to 14.3% ± 7.2 (P = 0.0014). Although, patients with a pre-phlebotomy PVI of >14% required more crystalloid replacement (11 ± 9.4 mL/kg) than those with a PVI ≤14% (5.3 ± 4.7 mL/kg), this was not significant (P = 0.06). In patients who received less crystalloid replacement during phlebotomy, PVI did show a significant increase. Additionally, the data suggests that patients with a pre-phlebotomy PVI >14% required greater fluid replacement than those with a PVI < 14%. Further research is needed to better delineate the utility of PVI in this unique group of patients.

The role of different anesthetic techniques in altering the stress response during cardiac surgery in children: a prospective, double-blinded, and randomized study.

OBJECTIVES: Our goal was to evaluate the role of three anesthetic techniques in altering the stress response in children undergoing surgery for repair of congenital heart diseases utilizing cardiopulmonary bypass in the setting of fast tracking or early tracheal extubation. Furthermore, we wanted to evaluate the correlation between blunting the stress response and the perioperative clinical outcomes. DESIGN: Prospective, randomized, double-blinded study. SETTING: Single center from December 2008 to May of 2011. PATIENTS: Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied between ages 30 days to 3 years old who were scheduled to undergo repair for a ventricular septal defect, atrioventricular septal defect, or Tetralogy of Fallot. METHODS: Children undergoing surgical repair of congenital heart disease were randomized to receive low-dose fentanyl (10 mcg/kg; low-dose fentanyl), high-dose fentanyl (25mcg/kg; high-dose fentanyl), or low-dose fentanyl plus dexmedetomidine (as a 1 mcg/kg loading dose followed by infusion at 0.5mcg/kg/hr until separation from cardiopulmonary bypass. In addition, patients received a volatile anesthetic agent as needed to maintain hemodynamic stability. Blood samples were tested for metabolic, hormonal and cytokine markers at baseline, after sternotomy, after the start of cardiopulmonary bypass, at the end of the procedure and at 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied. Subjects in the low-dose fentanyl plus placebo group had significantly higher levels of adrenocorticotropic hormone, cortisol, glucose, lactate, and epinephrine during the study period. The lowest levels of stress markers were seen in the high-dose fentanyl plus placebo group both over time (adrenocorticotropic hormone, p= 0.01; glucose, p = 0.007) and at individual time points (cortisol and lactate at the end of surgery, epinephrine poststernotomy; p < 0.05). Subjects in the low-dose fentanyl plus dexmedetomidine group had lower lactate levels at the end of surgery compared with the low-dose fentanyl plus placebo group (p < 0.05). Although there were no statistically significant differences in plasma cytokine levels between the three groups, the low-dose fentanyl plus placebo group had significantly higher interleukin-6:interleukin-10 ratio at 24 hours postoperatively (p < 0.0001). In addition, when compared with the low-dose fentanyl plus placebo group, the low-dose fentanyl plus dexmedetomidine group showed a lower norepinephrine level from baseline at poststernotomy, after the start of cardiopulmonary bypass, and at the end of surgery (p ≤ 0.05). Subjects in the low-dose fentanyl plus placebo group had more postoperative narcotic requirement (p = 0.004), higher prothrombin time (p ≤ 0.03), and more postoperative chest tube output (p < 0.05). Success of fast tracking was not significantly different between groups (low-dose fentanyl plus placebo 75%, high-dose fentanyl plus placebo 82%, low-dose fentanyl plus dexmedetomidine 93%; p = 0.39). CONCLUSIONS: The use of low-dose fentanyl was associated with the greatest stress response, most coagulopathy, and highest transfusion requirement among our cohorts. Higher dose fentanyl demonstrated more favorable blunting of the stress response. When compared with low-dose fentanyl alone, the addition of dexmedetomidine improved the blunting of the stress response, while achieving better postoperative pain control.

Length of stay and treatment-related complications are similar in pediatric and AYA patients with bone sarcoma in United States children's hospitals.

BACKGROUND: Adolescent and young adult (AYA) cancer patients have been shown to have unique clinical characteristics and inferior outcomes compared to younger patients. More than 2,500 new bone sarcomas are diagnosed yearly in the US, many of whom are AYAs treated at pediatric hospitals. Pediatric providers must understand the impact of increasing age on complications, costs, and outcomes. The study set-out to determine if AYA patients with bone sarcomas have increased healthcare utilization and treatment-related complications as compared to younger patients. PROCEDURE: Data were obtained from the Pediatric Health Information System for bone sarcoma admissions at 41 US children's hospitals from 2006 to 2010. Patient demographics and morbidities were compared in patients 0-14 and 15-28 years using two sample t-tests, Wilcoxon two sample tests, or chi-squared tests. RESULTS: We identified 835 pediatric and 562 AYA patients with bone sarcomas. Mean length of stay (LOS) was comparable between age groups (4.6 and 4.8 days, P = 0.46), although AYA patients had greater mean pharmaceutical charges ($18,124 vs. $13,637, P < 0.0001). Common treatment-related complications were similar between groups, with the exceptions that febrile neutropenia admissions were more likely in younger patients, and thrombosis, renal failure, and pain were more common in AYA patients. CONCLUSIONS: In US children's hospitals, AYA patients with sarcomas do not have prolonged LOS or an increased risk of the most common treatment-related complications as compared to younger patients. Chronic pain appears to be a greater burden in AYA patients, and may account for their higher inpatient pharmaceutical costs.

Metabolic syndrome and endocrine dysfunctions after HSCT in children.

MS and endocrine dysfunction(s) are common well-recognized complications after HSCT. We retrospectively analyzed our data on 160 patients with a median age at transplant of five yr (0.3-23), who had been followed for a median of seven yr (range 3-18) at Nationwide Children's Hospital after transplant. Dyslipidemia and MS were seen in 13% and 7.5% patients, respectively, and 58% of these patients were <20 yr of age. Twelve patients met the criteria for diagnosis of MS, but four of these did not meet the International Diabetic Federation or WHO criteria. Variation in the diagnostic criteria for MS leading to underdiagnosis is discussed. Female gonadal failure (27%) and hypothyroidism (21%) were the most common endocrine dysfunctions, followed by short stature and GH deficiency (17%) each. TBI and younger age at HSCT were associated with the highest burden of long-term effects, and female sex was more significantly associated with MS-related dysfunction (p < 0.05). Uniform diagnostic criteria for MS and close follow-up after transplant are important for the early diagnosis and management of these late effects, thereby improving the overall quality of life of these patients.